Ask AI
Back Back
Overcoming Obstacles in Obesity

CE / CME

Breaking Barriers in Obesity Care: Applying Emerging Evidence to Primary Care Practice

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

ABIM MOC: maximum of 1.00 Medical Knowledge MOC point

Physicians: maximum of 1.00 AMA PRA Category 1 Credit™

Nurse Practitioners/Nurses: 1.00 Nursing contact hour

Released: December 10, 2025

Expiration: December 09, 2026

Christopher Weber
Christopher Weber, MD, FAAP, FACP, CSCS, dABOM, FOMA
CME/CE Information

Activity

Progress
1 2 3
Course Completed

STEP UP: Semaglutide 7.2 mg in Patients With Obesity

Next, we will discuss new evidence related to approved indications for incretin-based AOMs, beginning with the STEP UP trial.

Semaglutide is currently available to treat obesity at a dose of 2.4 mg via subcutaneous (SC) injection. The STEP UP trial investigated an increased dose of 7.2 mg SC for patients with obesity, compared to the standard of care dose and to placebo (NCT05646706).5

Download

STEP UP: Outcomes

At 72 weeks, investigators reported that the mean weight loss with 7.2 mg SC semaglutide was 18.7%, compared to 15.6% weight loss with 2.4 mg SC. Of importance, patients who reached both a BMI <27 and a waist-to-height ratio <0.53 were more likely to reach a low-risk cardiometabolic state. Another fascinating aspect of this study is that, as quantified by sit-to-stand repetitions, there was no significant difference between the placebo group and the semaglutide intervention group in muscle function. This suggests that treatment with semaglutide preserves muscle function.5-8

Download

STEP UP: Differences in Responses to Semaglutide

Another key aspect of this study that I want to highlight is the differences in patient response to semaglutide, as it contributes to our knowledge about individual response to obesity treatment.

Among patients who were randomized to 7.2 mg SC, 669 were able to complete the trial on this dose. However, 66 people randomized to 7.2 mg underwent dose reductions to 2.4 mg due to adverse events (AEs) or sufficient efficacy with the lower dose, and 144 participants completed the trial with doses even less than 2.4 mg.9

Despite the variance in dosage, by the end of the trial, each group of patients had lost a comparable amount of weight. This suggests that individuals respond differently to semaglutide—some people may need a higher dose, while others can lose comparable weight with lower doses.9

Download

SCORE—Primary Prevention Study: Semaglutide 2.4 mg in Patients With Overweight or Obesity and ASCVD Risk Factors

The SCORE trial, a primary prevention population study utilizing 2016-2024 data from the US Komodo research database, is another key study of semaglutide.10

Here, investigators specifically assessed people with overweight or obesity, aged 45 years or older, who used semaglutide 2.4 mg SC and who did not have ASCVD, but did have at least 3 ASCVD risk factors. People were followed for an average of 9 months.10

The 2 main outcomes of this study were MACE: A revised 3-point MACE comprised of myocardial infarction, stroke, and all-cause mortality, and a revised 5-point MACE, encompassing myocardial infarction, stroke, all-cause mortality, and coronary revascularization or hospitalization for heart failure.10

Treatment with semaglutide was associated with a significant 35% reduction in the 5-point MACE and 41% reduction in the 3-point MACE. This shows that semaglutide reduces the risk of ASCVD events for people who are at higher risk but do not yet have ASCVD.10

Download

SURMOUNT-1 Cohort Analysis: Tirzepatide in Patients With MC4R Deficiency–Related Obesity

New evidence has also arisen for tirzepatide from a cohort analysis of the SURMOUNT-1 trial. This subset analysis assessed the efficacy of tirzepatide for people with mutations in melanocortin 4 receptor (MC4R), which is involved in appetite regulation and associated with increased risk for obesity.11,12

Among the 32 participants who had MC4R mutations, responses to tirzepatide were very comparable to participants who did not have an MC4R mutation: A mean change in body weight of -18.3% by at the end of the study for people who had the mutation, compared to -19.9% weight loss for people who did not.11

Of note, similar results have been shown with liraglutide. This suggests that GLP-1 receptor agonists, or at least tirzepatide and liraglutide, may be effective in people with homozygous MC4R mutations, especially when bariatric surgery is not effective.11,12

Download

SURMOUNT-OSA Post Hoc Analyses: OSA Measures Improved With Greater Tirzepatide-Induced Weight Loss

Continuing discussion of tirzepatide, let us look at the SURMOUNT-OSA post hoc analysis evaluating the effect of tirzepatide on measures of OSA severity with weight reduction.13

SURMOUNT-OSA consisted of 2 randomized, double-blind, placebo-controlled studies enrolling participants with moderate to severe OSA. Participants in the first study were not on positive airway pressure, whereas participants in the second study were.13

Both studies demonstrated significant improvements in the AHI, or the severity of OSA, with more dramatic improvements associated with greater weight loss.13

Download

Potential Economic Benefits With Incretin-Based AOMs

As encouraging as these new data are, there is still much discussion about the costs of AOMs and their economic impact. Common questions include: What is the return on investment? What are the cost savings? Are there cost savings at all?

One example of the economic impact of these interventions is the Komodo Health database study on the real-world impact of semaglutide for patients with high risk for CVD, which was discussed earlier. A retrospective analysis of this study showed an all-cause cost saving of $3870 per patient per year, and $3842 for obesity-related cost savings. Most of the savings here were driven by lower hospitalization rates, particularly a 35% reduction in inpatient visit rates.14

Another example of cost savings with these therapies comes from the SURMOUNT-1 trial with tirzepatide. In this study, investigators found cost savings of between $2590 and $3330 per person over the period of the trial, which was 176 weeks.15

In all, these studies demonstrate that the health benefits of these therapies are potentially associated with economic benefits as well.14,15 

Download

Case 1: Your patient is considering an incretin-based therapy for obesity management. They do not have established ASCVD, but there is a family history. They’d like to know whether an incretin-based therapy will reduce their ASCVD risk. How would you counsel them?

Case 2: Your patient is 27 years old, began experiencing weight gain in early childhood, and has had little or no success with lifestyle-based weight loss efforts throughout their life. Genetic testing has revealed that they are a carrier for a pathogenic MC4R mutation. How would you counsel them regarding obesity management?

Key Points for Individualizing Obesity Care: Recent Evidence on Approved Incretin-Based AOMs

To summarize the highlights of what we have touched on so far:

The STEP UP trial demonstrated the effectiveness of a 7.2 mg dose of semaglutide vs placebo, with preservation of muscle function. Of note, individual responses to semaglutide varied, with some patients able to achieve weight loss with a dose of 2.4 mg or less, while others required 7.2 mg.

Then, the SCORE primary prevention population study showed reduction in primary CV event risk with semaglutide treatment in a real-world setting. This is particularly impactful because efficacy in randomized controlled trials does not always translate to real-world results. Clinical trial settings are a much more well-controlled environment than the real world, usually with rigorous monitoring. Retrospective, real-world studies can provide a different perspective on things. It is impressive to know that an intervention such as semaglutide is actually lowering the risk for CVD in the real world despite all the challenges that come with it.

Finally, the cohort analysis of the SURMOUNT-1 trial showed that tirzepatide is effective in patients with MC4R mutations. MC4R mutations are relatively rare, but it is encouraging to know that advances are being made in personalizing obesity treatment with these medications.

Download
BACK | NEXT